Substantial evidence now exists to support earlier hopes that all night electroencephalographic sleep studies supplemented by psychological measurements, motor activity monitoring and clinical psychopharmacologic techniques will add an important dimension to the differential diagnosis and treatment of depression. We plan to test the following in 140 patients requiring hospitalization consecutively admitted to the Clinical Research Unit with a diagnosis of major depressive disorder: (1) that the indices derived from sleep parameters together with other psychobiologic measurements can substantially improve treatment response prediction by delineating the psychobiologic profile of various depressive subtypes; (2) more specifically, that a constellation of REM sleep measures predicts response to tricyclic antidepressants with a high degree of probability; (3) that specific neuroendocrine profiles during sleep are abnormal in depressive states, correlate with particular sleep abnormalities and can add to the precision of the psychobiologic profile in depression for both diagnosis and treatment prediction; (4) that clinical relapse and remission in depressive states are associated with sleep changes which may precede, coincide with, or even lag behind such changes and; (5) that certain sleep abnormalities (e.g., short REM latency) may persist even during periods of clinical remission as psychobiologic "markers." This "probe" into the depressed state represents the major emphasis of our studies which seek to correlate sleep parameters and neuroendocrine secretion in depression, both with a view toward specifying possible mechanisms of sleep disturbance in depression and providing new criteria for diagnosis and treatment. In addition, we expect that animal studies can increase our understanding of chronic sleep-tricyclic drug interactions and of the interrelationship between "hyperresponsive" cholinergic stimulation and EEG sleep.